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1.
PLoS Med ; 21(5): e1004390, 2024 May 06.
Artigo em Inglês | MEDLINE | ID: mdl-38709851

RESUMO

BACKGROUND: When research evidence is limited, inconsistent, or absent, healthcare decisions and policies need to be based on consensus among interested stakeholders. In these processes, the knowledge, experience, and expertise of health professionals, researchers, policymakers, and the public are systematically collected and synthesised to reach agreed clinical recommendations and/or priorities. However, despite the influence of consensus exercises, the methods used to achieve agreement are often poorly reported. The ACCORD (ACcurate COnsensus Reporting Document) guideline was developed to help report any consensus methods used in biomedical research, regardless of the health field, techniques used, or application. This explanatory document facilitates the use of the ACCORD checklist. METHODS AND FINDINGS: This paper was built collaboratively based on classic and contemporary literature on consensus methods and publications reporting their use. For each ACCORD checklist item, this explanation and elaboration document unpacks the pieces of information that should be reported and provides a rationale on why it is essential to describe them in detail. Furthermore, this document offers a glossary of terms used in consensus exercises to clarify the meaning of common terms used across consensus methods, to promote uniformity, and to support understanding for consumers who read consensus statements, position statements, or clinical practice guidelines (CPGs). The items are followed by examples of reporting items from the ACCORD guideline, in text, tables, and figures. CONCLUSIONS: The ACCORD materials-including the reporting guideline and this explanation and elaboration document-can be used by anyone reporting a consensus exercise used in the context of health research. As a reporting guideline, ACCORD helps researchers to be transparent about the materials, resources (both human and financial), and procedures used in their investigations so readers can judge the trustworthiness and applicability of their results/recommendations.

2.
J Clin Epidemiol ; : 111392, 2024 May 11.
Artigo em Inglês | MEDLINE | ID: mdl-38740313

RESUMO

OBJECTIVE: To assess to what extent the overall quality of evidence indicates changes to observed intervention effect estimates when new data become available. STUDY DESIGN AND SETTING: We conducted a meta- epidemiological study. We obtained evidence from meta-analyses of randomized trials of Cochrane reviews addressing the same healthcare question that was updated with inclusion of additional data between January 2016 and May 2021. METHODS: We extracted the reported effect estimates with 95% confidence intervals from meta-analyses and corresponding GRADE (Grading of Recommendations Assessment, Development, and Evaluation) assessments of any intervention comparison for the primary outcome in the first and the last updated review version. We considered the reported overall quality (certainty) of evidence (CoE) and specific evidence limitations (no, serious or very serious for risk of bias, imprecision, inconsistency, and/or indirectness). We assessed the change in pooled effect estimates between the original and updated evidence using the ratio of odds ratio (ROR), absolute ROR (aROR), ratio of standard errors (RoSE), direction of effects, and level of statistical significance. RESULTS: High CoE without limitations characterized 19.3% (n=29) out of 150 included original Cochrane reviews. The update with additional data did not systematically change the effect estimates (mean ROR 1.00; 95%CI 0.99-1.02), which deviated 1.06-fold from the older estimates (median aROR; IQR: 1.01-1.15), gained precision (median RoSE 0.87; IQR 0.76-1.00), and maintained the same direction with the same level of statistical significance in 93% (27 of 29) of cases. Lower CoE with limitations characterized 121 original reviews and graded as moderate CoE in 30.0% (45 of 150), low CoE in 32.0% (48 of 150), and very low CoE in 18.7% (28 of 150) reviews. Their update had larger absolute deviations (median aROR 1.12 to 1.33) and larger gains in precision (median RoSE 0.78 to 0.86) without clear and consistent differences between these categories of CoE. Changes in effect direction or statistical significance were also more common in the lower quality evidence, again with a similar extent across categories (without change in 75.6%, 64.6%, and 75.0% for moderate, low, very low CoE). As limitations increased, effect estimates deviated more (aROR 1.05 with zero, 1.11 with one, 1.25 with two, 1.24 with three limitations) and changes in direction or significance became more frequent (93.2% stable with no limitations, 74.5% with one, 68.2% with two, and 61.5% with three limitations). CONCLUSIONS: High-quality evidence without methodological deficiencies is trustworthy and stable, providing reliable intervention effect estimates when updated with new data. Evidence of moderate and lower quality may be equally prone to being unstable and cannot indicate if available effect estimates are true, exaggerated, or underestimated.

3.
Gynecol Oncol ; 185: 58-67, 2024 Feb 17.
Artigo em Inglês | MEDLINE | ID: mdl-38368814

RESUMO

OBJECTIVE: Adenoid cystic carcinoma (AdCC) of the Bartholin's gland (AdCC-BG) is a very rare gynecologic vulvar malignancy. AdCC-BGs are slow-growing but locally aggressive and are associated with high recurrence rates. Here we sought to characterize the molecular underpinning of AdCC-BGs. METHODS: AdCC-BGs (n = 6) were subjected to a combination of RNA-sequencing, targeted DNA-sequencing, reverse-transcription PCR, fluorescence in situ hybridization (FISH) and MYB immunohistochemistry (IHC). Clinicopathologic variables, somatic mutations, copy number alterations and chimeric transcripts were assessed. RESULTS: All six AdCC-BGs were biphasic, composed of ductal and myoepithelial cells. Akin to salivary gland and breast AdCCs, three AdCC-BGs had the MYB::NFIB fusion gene with varying breakpoints, all of which were associated with MYB overexpression by IHC. Two AdCC-BGs were underpinned by MYBL1 fusion genes with different gene partners, including MYBL1::RAD51B and MYBL1::EWSR1 gene fusions, and showed MYB protein expression. Although the final AdCC-BG studied had MYB protein overexpression, no gene fusion was identified. AdCC-BGs harbored few additional somatic genetic alterations, and only few mutations in cancer-related genes were identified, including GNAQ, GNAS, KDM6A, AKT1 and BCL2, none of which were recurrent. Two AdCC-BGs, both with a MYB::NFIB fusion gene, developed metastatic disease. CONCLUSIONS: AdCC-BGs constitute a convergent phenotype, whereby activation of MYB or MYBL1 can be driven by the MYB::NFIB fusion gene or MYBL1 rearrangements. Our observations further support the notion that AdCCs, irrespective of organ site, constitute a genotypic-phenotypic correlation. Assessment of MYB or MYBL1 rearrangements may be used as an ancillary marker for the diagnosis of AdCC-BGs.

4.
PLoS Med ; 21(1): e1004326, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-38261576

RESUMO

BACKGROUND: In biomedical research, it is often desirable to seek consensus among individuals who have differing perspectives and experience. This is important when evidence is emerging, inconsistent, limited, or absent. Even when research evidence is abundant, clinical recommendations, policy decisions, and priority-setting may still require agreement from multiple, sometimes ideologically opposed parties. Despite their prominence and influence on key decisions, consensus methods are often poorly reported. Our aim was to develop the first reporting guideline dedicated to and applicable to all consensus methods used in biomedical research regardless of the objective of the consensus process, called ACCORD (ACcurate COnsensus Reporting Document). METHODS AND FINDINGS: We followed methodology recommended by the EQUATOR Network for the development of reporting guidelines: a systematic review was followed by a Delphi process and meetings to finalize the ACCORD checklist. The preliminary checklist was drawn from the systematic review of existing literature on the quality of reporting of consensus methods and suggestions from the Steering Committee. A Delphi panel (n = 72) was recruited with representation from 6 continents and a broad range of experience, including clinical, research, policy, and patient perspectives. The 3 rounds of the Delphi process were completed by 58, 54, and 51 panelists. The preliminary checklist of 56 items was refined to a final checklist of 35 items relating to the article title (n = 1), introduction (n = 3), methods (n = 21), results (n = 5), discussion (n = 2), and other information (n = 3). CONCLUSIONS: The ACCORD checklist is the first reporting guideline applicable to all consensus-based studies. It will support authors in writing accurate, detailed manuscripts, thereby improving the completeness and transparency of reporting and providing readers with clarity regarding the methods used to reach agreement. Furthermore, the checklist will make the rigor of the consensus methods used to guide the recommendations clear for readers. Reporting consensus studies with greater clarity and transparency may enhance trust in the recommendations made by consensus panels.


Assuntos
Pesquisa Biomédica , Consenso , Humanos , Lista de Checagem , Políticas , Confiança
5.
Int J Gynecol Cancer ; 2023 Dec 07.
Artigo em Inglês | MEDLINE | ID: mdl-38088182

RESUMO

OBJECTIVE: The prognostic significance of isolated tumor cells (≤0.2 mm) in sentinel lymph nodes (SLNs) of endometrial cancer patients is still unclear. Our aim was to assess the prognostic value of isolated tumor cells in patients with low risk endometrial cancer who underwent SLN biopsy and did not receive adjuvant therapy. Outcomes were compared with node negative patients. METHODS: Patients with SLNs-isolated tumor cells between 2013 and 2019 were identified from 15 centers worldwide, while SLN negative patients were identified from Mayo Clinic, Rochester, between 2013 and 2018. Only low risk patients (stage IA, endometrioid histology, grade 1 or 2) who did not receive any adjuvant therapy were included. Primary outcomes were recurrence free, non-vaginal recurrence free, and overall survival, evaluated with Kaplan-Meier methods. RESULTS: 494 patients (42 isolated tumor cells and 452 node negative) were included. There were 21 (4.3%) recurrences (5 SLNs-isolated tumor cells, 16 node negative); recurrence was vaginal in six patients (1 isolated tumor cells, 5 node negative), and non-vaginal in 15 (4 isolated tumor cells, 11 node negative). Median follow-up among those without recurrence was 2.3 years (interquartile range (IQR) 1.1-3.0) and 2.6 years (IQR 0.6-4.2) in the SLN-isolated tumor cell and node negative patients, respectively. The presence of SLNs-isolated tumor cells, lymphovascular space invasion, and International Federation of Obstetrics and Gynecology (FIGO) grade 2 were significant risk factors for recurrence on univariate analysis. SLN-isolated tumor cell patients had worse recurrence free survival (p<0.01) and non-vaginal recurrence free survival (p<0.01) compared with node negative patients. Similar results were observed in the subgroup of patients without lymphovascular space invasion (n=480). There was no difference in overall survival between the two cohorts in the full sample and the subset excluding patients with lymphovascular space invasion. CONCLUSIONS: Patients with SLNs-isolated tumor cells and low risk profile, without adjuvant therapy, had a significantly worse recurrence free survival compared with node negative patients with similar risk factors, after adjusting for grade and excluding patients with lymphovascular space invasion. However, the presence of SLNs-isolated tumor cells was not associated with worse overall survival.

6.
BMJ ; 383: 2505, 2023 10 31.
Artigo em Inglês | MEDLINE | ID: mdl-37907212
7.
bioRxiv ; 2023 Jun 29.
Artigo em Inglês | MEDLINE | ID: mdl-37425747

RESUMO

Effective communication hinges on a mutual understanding of word meaning in different contexts. The embedding space learned by large language models can serve as an explicit model of the shared, context-rich meaning space humans use to communicate their thoughts. We recorded brain activity using electrocorticography during spontaneous, face-to-face conversations in five pairs of epilepsy patients. We demonstrate that the linguistic embedding space can capture the linguistic content of word-by-word neural alignment between speaker and listener. Linguistic content emerged in the speaker's brain before word articulation, and the same linguistic content rapidly reemerged in the listener's brain after word articulation. These findings establish a computational framework to study how human brains transmit their thoughts to one another in real-world contexts.

8.
J Ovarian Res ; 16(1): 122, 2023 Jun 27.
Artigo em Inglês | MEDLINE | ID: mdl-37370140

RESUMO

Poly-ADP Ribose Polymerase (PARP) targeted therapy is clinically approved for the treatment of homologous recombination (HR) repair deficient tumors. The remarkable success of this therapy in the treatment of HR repair deficient cancers has not translated to HR-proficient cancers. Our studies identify the novel role of non-receptor lymphocyte-specific protein tyrosine kinase (LCK) in the regulation of HR repair in endometrioid epithelial ovarian cancer (eEOC) model. We show that DNA damage leads to direct interaction of LCK with the HR repair proteins RAD51 and BRCA1 in a kinase dependent manner RAD51 and BRCA1 stabilization. LCK expression is induced and activated in the nucleus in response to DNA damage insult. Disruption of LCK expression attenuates RAD51, BRCA1, and BRCA2 protein expression by hampering there stability and results in inhibition of HR-mediated DNA repair including suppression of RAD51 foci formation, and augmentation of γH2AX foci formation. In contrast LCK overexpression leads to increased RAD51 and BRCA1 expression with a concomitant increase in HR DNA damage repair. Importantly, attenuation of LCK sensitizes HR-proficient eEOC cells to PARP inhibitor in cells and pre-clinical mouse studies. Collectively, our findings identify a novel therapeutic strategy to expand the utility of PARP targeted therapy in HR proficient ovarian cancer.


Assuntos
Carcinoma Endometrioide , Neoplasias Ovarianas , Animais , Feminino , Humanos , Camundongos , Proteína BRCA1/genética , Carcinoma Endometrioide/tratamento farmacológico , Carcinoma Epitelial do Ovário/tratamento farmacológico , Linhagem Celular Tumoral , Dano ao DNA , Reparo do DNA , Recombinação Homóloga , Neoplasias Ovarianas/tratamento farmacológico , Neoplasias Ovarianas/genética , Neoplasias Ovarianas/patologia , Inibidores de Poli(ADP-Ribose) Polimerases/farmacologia , Inibidores de Poli(ADP-Ribose) Polimerases/uso terapêutico , Rad51 Recombinase/genética , Rad51 Recombinase/metabolismo
9.
Dalton Trans ; 52(17): 5433-5437, 2023 May 02.
Artigo em Inglês | MEDLINE | ID: mdl-37070223

RESUMO

The chemistry of the tris-carbene anion phenyltris(3-alkyl-imidazoline-2-yliden-1-yl)borate, [C3Me]- ligand, is initiated for f-block metal cations. Neutral, molecular complexes of the form Ln(C3)2I are formed for cerium(III), while a separated ion pair [Ln(C3)2]I forms for ytterbium(III). DFT/QTAIM computational analyses of the complexes and related tridentate tris(pyrazolyl)borate (Tp) - supported analogs demonstrates the anticipated strength of the σ donation and confirms greater covalency in the metal-carbon bonds of the [C3Me]- complexes in comparison with those in the TpMe,Me complexes. The DFT calculations demonstrate the crucial role of THF solvent in accurately reproducing the contrasting molecular and ion-pair geometries observed experimentally for the Ce and Yb complexes.

10.
Am J Surg Pathol ; 47(5): 580-588, 2023 05 01.
Artigo em Inglês | MEDLINE | ID: mdl-36939053

RESUMO

Among gynecologic cancers, uterine serous carcinoma (USC) has been shown to be human epidermal growth factor receptor 2 (HER2) amplified and trastuzumab has been included in the recent National Comprehensive Cancer Network (NCCN) guidelines for treatment of advanced stage or recurrent USC with HER2 overexpression/amplification. There is limited literature suggesting that a subset of high-grade endometrioid carcinomas with aberrant p53 expression may also be HER2 amplified and these patients could benefit from the addition of targeted therapy. We identified 59 p53-aberrant (mismatch repair proficient) FIGO 3 endometrioid carcinomas of the uterus. HER2 immunohistochemistry was performed in all 59 tumors and HER2 fluorescence in situ hybridization (FISH) was performed in 52 of the 59 cases. Four of the 59 cases were HER2 3+ by immunohistochemistry (6.7%), using the American Society of Clinical Oncology/College of American Pathologists (ASCO/CAP) 2007, 2013, and 2018 criteria. HER2 FISH was performed in 3 of the 4 cases and was amplified in all 3. Nine, 8, and 7 tumors showed 2+ HER2 staining when applying 2018, 2013, and 2007 criteria, respectively, FISH was performed in 7 tumors and none were amplified. An additional 4 cases did not perfectly meet the 2018 ASCO/CAP criteria but were assigned a score of 2+, none were amplified by HER2 FISH. The remaining 42 cases showed 1+ or no staining for HER2, FISH was successfully performed in 38 tumors and none showed amplification. Approximately half of the tumors fulfilled criteria for HER2-low or HER2-very low (10 HER2-low and 20 HER2-very low). Our data shows that a subset of p53-aberrant high-grade endometrial endometrioid carcinoma express HER2 and these patients may benefit from the addition of targeted therapy. The role of targeted therapy in HER2-low gynecologic carcinoma is currently unexplored.


Assuntos
Neoplasias da Mama , Carcinoma Endometrioide , Cistadenocarcinoma Seroso , Neoplasias Uterinas , Humanos , Feminino , Amplificação de Genes , Carcinoma Endometrioide/genética , Carcinoma Endometrioide/terapia , Proteína Supressora de Tumor p53/genética , Proteína Supressora de Tumor p53/metabolismo , Hibridização in Situ Fluorescente , Receptor ErbB-2 , Neoplasias Uterinas/patologia , Cistadenocarcinoma Seroso/genética , Neoplasias da Mama/genética , Biomarcadores Tumorais/genética
12.
Int J Gynecol Pathol ; 42(5): 443-450, 2023 Sep 01.
Artigo em Inglês | MEDLINE | ID: mdl-36731037

RESUMO

Poorly differentiated malignant neoplasms involving the gynecologic tract routinely include a poorly differentiated endometrial carcinoma (EC) in the differential diagnosis. Some nuclear lineage/site-specific immunohistochemical markers are utilized in this diagnostic setting including SATB2, cyclin D1, SALL4, and BCOR, but their specificity and use in small samples are not clear across the spectrum of ECs. Cases of undifferentiated/dedifferentiated endometrial carcinomas (UEC/DDEC), clear cell carcinoma (CCC), uterine serous carcinoma (USC), FIGO grade 3 endometrial endometrioid carcinoma (EEC), and uterine carcinosarcoma (UCS) were identified and diagnoses confirmed. Whole-section immunohistochemical stains for SATB2, cyclin D1, SALL4, BCOR, and PAX8 were performed. A total of 113 cases were utilized: 15 CCC, 26 EEC, 19 UCS, 22 USC, and 31 UEC/DDEC. Cases were distributed across both low (49%) and high (51%) FIGO clinical stages. SATB2 was expressed by UCS (8/19, 42%), EEC (10/26, 38%), UEC/DDEC (11/30, 37%), and USC (6/22, 27%). Cyclin D1 was expressed by EEC (24/26, 92%), USC (17/22, 77%), UEC/DDEC (15/20 EEC component, 75%; 22/30 UEC, 73%), UCS (10/16 carcinoma, 63%; 11/19 sarcoma, 58%), and CCC (8/15, 53%). SALL4 was expressed most frequently by UEC/DDEC (12/30, 40%), but also USC (7/22, 32%), EEC (5/26, 19%), and UCS (4/16 carcinoma, 25%; 3/19 sarcoma, 16%). BCOR was expressed at low levels in 2 USC, 2 UEC/DDEC, and 2 UCS. PAX8 was generally positive but showed lower expression in UEC/DDEC (17/30, 57%) and in the sarcomatous portions of UCS (6/19, 32%). SATB2, cyclin D1, SALL4, and BCOR stain variable numbers of poorly-differentiated EC and must be carefully interpreted within morphologic and clinical context.


Assuntos
Neoplasias do Endométrio , Proteínas de Ligação à Região de Interação com a Matriz , Neoplasias Uterinas , Feminino , Humanos , Carcinoma Endometrioide/genética , Carcinoma Endometrioide/patologia , Ciclina D1 , Neoplasias do Endométrio/genética , Neoplasias do Endométrio/patologia , Proteínas Proto-Oncogênicas , Proteínas Repressoras , Sarcoma , Fatores de Transcrição/metabolismo , Neoplasias Uterinas/genética , Neoplasias Uterinas/patologia
15.
JMIR Res Protoc ; 11(12): e36549, 2022 Dec 01.
Artigo em Inglês | MEDLINE | ID: mdl-36454625

RESUMO

BACKGROUND: The design of personal protective equipment (PPE) may affect well-being and clinical work. PPE as an integrated item may improve usability and increase adherence by healthcare professionals. Human factors design and safety may reduce occupational-acquired diseases. As an integrated PPE, a lightweight protective air-purifying respirator (L-PAPR) could be used during health procedures where healthcare professionals are exposed to airborne pathogens. The human factors affecting the implementation of alternative PPE such as L-PAPR have not been thoroughly studied. The population of interest is health care professionals, the intervention is the performance by PPE during tasks across the three PPE types 1.) N95 respirators and face shields, 2.)traditional powered air-purifying respirator(PAPR), and 3.) L-PAPR. The outcomes are user error, communications, safety, and end-user preferences. OBJECTIVE: This study will assess whether the L-PAPR improves health care professionals' comfort in terms of perceived workload and physical and psychological burden during direct patient care when compared with the traditional PAPR or N95 and face shield. This study also aims to evaluate human factors during the comparison of the use of L-PAPR with a combination of N95 respirators plus face shields or the traditional PAPRs. METHODS: This is an interventional randomized crossover quality improvement feasibility study consisting of a 3-site simulation phase with 10 participants per site and subsequent field testing in 2 sites with 30 participants at each site. The 3 types of respiratory PPE will be compared across medical tasks and while donning and doffing. We will evaluate the user's perceived workload, usability, usage errors, and heart rate. We will conduct semistructured interviews to identify barriers and enablers to implementation across each PPE type over a single continuous wear episode and observe interpersonal communications across conditions and PPE types. RESULTS: We expect the research may highlight communication challenges and differences in usability and convenience across PPE types along with error frequency during PPE use across PPE types, tasks, and time. CONCLUSIONS: The design of PPE may affect overall well-being and hinder or facilitate clinical work. Combining 2 pieces of PPE into a single integrated item may improve usability and reduce occupational-acquired diseases. The human factors affecting the implementation of an alternative PPE such as L-PAPR or PAPR have not been thoroughly studied. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): PRR1-10.2196/36549.

16.
Nat Commun ; 13(1): 5923, 2022 Oct 07.
Artigo em Inglês | MEDLINE | ID: mdl-36207297

RESUMO

Covalency involving the 5f orbitals is regularly invoked to explain the reactivity, structure and spectroscopic properties of the actinides, but the ionic versus covalent nature of metal-ligand bonding in actinide complexes remains controversial. The tetrakis 2,6-di-tert-butylphenoxide complexes of Th, U and Np form an isostructural series of crystal structures containing approximately tetrahedral MO4 cores. We show that up to 3 GPa the Th and U crystal structures show negative linear compressibility as the OMO angles distort. At 3 GPa the angles snap back to their original values, reverting to a tetrahedral geometry with an abrupt shortening of the M-O distances by up to 0.1 Å. The Np complex shows similar but smaller effects, transforming above 2.4 GPa. Electronic structure calculations associate the M-O bond shortening with a change in covalency resulting from increased contributions to the M-O bonding by the metal 6d and 5f orbitals, the combination promoting MO4 flexibility at little cost in energy.

17.
BMJ Open ; 12(9): e065154, 2022 09 08.
Artigo em Inglês | MEDLINE | ID: mdl-36201247

RESUMO

OBJECTIVE: To identify evidence on the reporting quality of consensus methodology and to select potential checklist items for the ACcurate COnsensus Reporting Document (ACCORD) project to develop a consensus reporting guideline. DESIGN: Systematic review. DATA SOURCES: Embase, MEDLINE, Web of Science, PubMed, Cochrane Library, Emcare, Academic Search Premier and PsycINFO from inception until 7 January 2022. ELIGIBILITY CRITERIA: Studies, reviews and published guidance addressing the reporting quality of consensus methodology for improvement of health outcomes in biomedicine or clinical practice. Reports of studies using or describing consensus methods but not commenting on their reporting quality were excluded. No language restrictions were applied. DATA EXTRACTION AND SYNTHESIS: Screening and data extraction of eligible studies were carried out independently by two authors. Reporting quality items addressed by the studies were synthesised narratively. RESULTS: Eighteen studies were included: five systematic reviews, four narrative reviews, three research papers, three conference abstracts, two research guidance papers and one protocol. The majority of studies indicated that the quality of reporting of consensus methodology could be improved. Commonly addressed items were: consensus panel composition; definition of consensus and the threshold for achieving consensus. Items least addressed were: public patient involvement (PPI); the role of the steering committee, chair, cochair; conflict of interest of panellists and funding. Data extracted from included studies revealed additional items that were not captured in the data extraction form such as justification of deviation from the protocol or incentives to encourage panellist response. CONCLUSION: The results of this systematic review confirmed the need for a reporting checklist for consensus methodology and provided a range of potential checklist items to report. The next step in the ACCORD project builds on this systematic review and focuses on reaching consensus on these items to develop the reporting guideline. PROTOCOL REGISTRATION: https://osf.io/2rzm9.


Assuntos
Lista de Checagem , Relatório de Pesquisa , Consenso , Humanos
18.
Cancer Res ; 82(24): 4654-4669, 2022 12 16.
Artigo em Inglês | MEDLINE | ID: mdl-36206317

RESUMO

Epithelial ovarian cancer (EOC) is the leading cause of gynecologic cancer death. Despite initial responses to intervention, up to 80% of patient tumors recur and require additional treatment. Retrospective clinical analysis of patients with ovarian cancer indicates antibiotic use during chemotherapy treatment is associated with poor overall survival. Here, we assessed whether antibiotic (ABX) treatment would impact growth of EOC and sensitivity to cisplatin. Immunocompetent or immunocompromised mice were given untreated control or ABX-containing (metronidazole, ampicillin, vancomycin, and neomycin) water prior to intraperitoneal injection with EOC cells, and cisplatin therapy was administered biweekly until endpoint. Tumor-bearing ABX-treated mice exhibited accelerated tumor growth and resistance to cisplatin therapy compared with control treatment. ABX treatment led to reduced apoptosis, increased DNA damage repair, and enhanced angiogenesis in cisplatin-treated tumors, and tumors from ABX-treated mice contained a higher frequency of cisplatin-augmented cancer stem cells than control mice. Stool analysis indicated nonresistant gut microbial species were disrupted by ABX treatment. Cecal transplants of microbiota derived from control-treated mice was sufficient to ameliorate chemoresistance and prolong survival of ABX-treated mice, indicative of a gut-derived tumor suppressor. Metabolomics analyses identified circulating gut-derived metabolites that were altered by ABX treatment and restored by recolonization, providing candidate metabolites that mediate the cross-talk between the gut microbiome and ovarian cancer. Collectively, these findings indicate that an intact microbiome functions as a tumor suppressor in EOC, and perturbation of the gut microbiota with ABX treatment promotes tumor growth and suppresses cisplatin sensitivity. SIGNIFICANCE: Restoration of the gut microbiome, which is disrupted following antibiotic treatment, may help overcome platinum resistance in patients with epithelial ovarian cancer. See related commentary by Hawkins and Nephew, p. 4511.


Assuntos
Microbioma Gastrointestinal , Neoplasias Ovarianas , Humanos , Feminino , Camundongos , Animais , Carcinoma Epitelial do Ovário/tratamento farmacológico , Carcinoma Epitelial do Ovário/patologia , Cisplatino/uso terapêutico , Estudos Retrospectivos , Recidiva Local de Neoplasia/tratamento farmacológico , Neoplasias Ovarianas/patologia , Antibacterianos/farmacologia
19.
Am J Infect Control ; 50(8): 878-884, 2022 08.
Artigo em Inglês | MEDLINE | ID: mdl-35908826

RESUMO

BACKGROUND: Face shields were widely used in 2020-2021 as facial personal protective equipment (PPE). Laboratory evidence about how protective face shields might be and whether real world user priorities and usage habits conflicted with best practice for maximum possible protection was lacking - especially in limited resource settings. METHODS: Relative protective potential of 13 face shield designs were tested in a controlled laboratory setting. Community and health care workers were surveyed in middle income country cities (Brazil and Nigeria) about their preferences and perspectives on face shields as facial PPE. Priorities about facial PPE held by survey participants were compared with the implications of the laboratory-generated test results. RESULTS: No face shield tested totally eliminated exposure. Head orientation and design features influenced the level of protection. Over 600 individuals were interviewed in Brazil and Nigeria (including 240 health care workers) in March-April 2021. Respondents commented on what influenced their preferred forms of facial PPE, how they tended to clean face shields, and their priorities in choosing a face cover product. Surveyed health care workers commonly bought personal protection equipment for use at work. CONCLUSIONS: All face shields provided some protection but none gave high levels of protection against external droplet contamination. Respondents wanted facial PPE that considered good communication, secure fixture, good visibility, comfort, fashion, and has validated protectiveness.


Assuntos
COVID-19 , Equipamento de Proteção Individual , COVID-19/prevenção & controle , Países em Desenvolvimento , Pessoal de Saúde , Humanos , Equipamentos de Proteção
20.
Am J Infect Control ; 50(8): 898-905, 2022 08.
Artigo em Inglês | MEDLINE | ID: mdl-35908829

RESUMO

BACKGROUND: Adherence to infection prevention and control (IPC) measures, including the proper use of protective personal equipment (PPE), in health care is complex and is influenced by many factors. Isolated interventions do not have the potential to achieve optimal PPE adherence and appropriate provision, leading to incomplete PPE implementation. OBJECTIVE: To map PPE implementation in health care with a focus on its barriers and facilitators. METHODS: A scoping review was conducted across 14 electronic databases using the Joanna Briggs Institute methodology. RESULTS: Seventy-four papers were included in the review. Findings were analyzed and synthesized into categories to match the Consolidated Framework for Implementation Research domains. The content was then synthesized into barriers for PPE implementation and interventions to address them. The main barriers were discomfort in clinical work; shortage, supply and logistics problems; inadequacies in facilities infrastructure, weakness in policies and communication procedures; and health workers' (HW) psychological issues and lack of preparedness. Implementation interventions reported were related to HW wellbeing assurance; work reorganization; IPC protocols; adoption of strategies to improve communication and HW training; and adoption of structural and organizational changes to improve PPE adherence. CONCLUSIONS: PPE implementation, which is critical IPC programs, involves multilevel transdisciplinary complexity. It relies on the development of context-driven implementation strategies to inform and harmonize IPC policy in collaboration with local and international health bodies.


Assuntos
Pessoal de Saúde , Equipamento de Proteção Individual , Atenção à Saúde , Instalações de Saúde , Pessoal de Saúde/psicologia , Humanos
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